2,2,6,6-Tetramethylpiperidine and its derivatives are important spin traps for labelling biological molecules. This is illustrated in a number of reviews as follows: J. F. W. Keana, Chemical Reviews, 78, 37 (1978); M. Dagonneau et al., Synthesis, 1984, 895; E. G. Rozantsev et al., Synthesis 1971, 401; and E. G. Rozantsev et al., Synthesis, 1971, 190.
Such compounds are also disclosed as inhibitors for preventing the premature polymerization of vinyl monomers as seen in U.S. Pat. No. 5,254,760.
The oxidation of 4-substituted 2,2,6,6-tetramethylpiperidines to the corresponding N-oxyl derivatives is known to occur by a number of different processes. U.S. Pat. No. 4,665,185 describes using tert-butyl hydroperoxide with transition metal (molybdenum) catalysts. G. Sosnovsky et al., Z. Naturforsch. 31b, 1376 (1976); J. Zakrzewski, J. Prakt. Chem., 327, 1011 (1985) and E. G. Rozantsev et al., Synthesis, 1971, 190 each teach the use of hydrogen peroxide with sodium tungstate catalyst. U.S. Pat. No. 5,416,215 teaches the use of hydrogen and selected divalent metal salts. M. E. Brik, Tetrahedron Letters, 36, 5519 (1995) teaches the oxidation of secondary amines to nitroxides using Oxone.RTM. (potassium peroxomonosulfate) in aqueous buffered solutions.
E. J. Rauckman et al., Syn. Communications 5(6), 409 (1975) describe inter alia the oxidation of secondary amines to nitroxides using catalytic amounts of sodium tungstate in the presence of acetonitrile, methanol, hydrogen peroxide and sodium bicarbonate at room temperature for two days to give the oxyl compound in a yield of 85%. The required presence of the known sodium tungstate catalyst clearly differentiates the Rauckman process from the instant process where no catalyst is present.
J. Zakrzewski, J. prakt. Chem., 327(6), 1011 (1985) does teach that 30% hydrogen peroxide in the presence of a three molar excess of sodium carbonate gives the oxyl compound in a yield of 73% after two days. The instant process requires no catalyst and gives the oxyl compound in very high conversion in less than five hours. The instant process is clearly different from the process of Zakrzewski.
In a copending application Ser. No. 08/555,823, a process is described involving the use of an environmentally safe and friendly catalyst which avoids the presence of transition metals in waste waters. While sodium bicarbonate and sodium carbonate are easily handled, are economically inexpensive and cause no adverse environmental conditions, the instant process also gives the desired N-oxyl compounds in high yields and conversions without the use for costly and environmetally hazardous transition metals or divalent metal ions.
The instant process involves a still simpler method to prepare the desired N-oxyl compound by using hydrogen peroxide in the absence of any catalyst at a moderate temperature. There is no undesirable waste by-product of the instant process.